Search

Ziyang Sang, Hui-Fang Chen, Jerf WK Yeung, Leilei Xu Department of Social and Behavioural Sciences, City University of Hong Kong, Kowloon, Hong Kong Special Administrative RegionCorrespondence: Hui-Fang Chen, Department of Social and Behavioural Sciences, City University of Hong Kong, 83 Tat Chee Ave, Kowloon, Hong Kong Special Administrative Region, Tel +852 3442297, Fax +852 34420283, Email hfchen@cityu.edu.hkPurpose: This study investigated the mechanism underlying the association between intolerance of uncertainty and mobile phone addiction among Chinese overseas students during the COVID-19 pandemic by examining the mediating roles of perceived stress and rumination.Patients and Methods: An online questionnaire survey was distributed via social media platforms popular in mainland China. The items collected demographic information and assessed intolerance of uncertainty, perceived stress, rumination, and mobile phone addiction. A total of 249 respondents completed the questionnaire.Results: The findings suggest a considerably high risk of mobile phone addiction in the study period among overseas Chinese students, as three-fourths of the participants may have been susceptible to mobile phone addiction according to the suggested cut-off point of the Chinese version of the Smartphone Addiction Scale–Short Form. Intolerance of uncertainty showed a significant positive direct effect on mobile phone addiction. The mediation analyses suggest that intolerance of uncertainty affected mobile phone addiction mainly through three pathways: the mediating effect of perceived stress, the mediating effect of rumination, and the chain mediating effect of perceived stress and rumination.Conclusion: This study enhances understanding of mobile phone addiction among Chinese overseas students and suggests the mediating roles of rumination and perceived stress in the relationship between intolerance of uncertainty and mobile phone addiction. The study also provides suggestions for interventions among Chinese students overseas.Keywords: vulnerability, mental health, health issues, internet

The finite element method(FEM)is a widely employed mathematical technique in mechanical research that divides an object into discrete and interacting finite elements. Medically, finite element analysis(FEA)enables the simulation of biomechanical experiments that are challenging to conduct. Orbital surgery poses significant challenges to ophthalmologists due to its inherent difficulty and steep learning curve. FEM enables the simulation and analysis of the mechanical properties of orbital tissue, offering a novel approach for diagnosing and treating orbital-related diseases. With technological advancements, FEM has significantly matured in the diagnosis and treatment of orbital diseases, becoming a popular area of research in orbital biomechanics. This paper reviewed the latest advancements in orbital FEM, encompassing the development of orbital FEA models, simulation of orbital structure, and its application in orbital-related diseases. Additionally, the limitations of FEM and future research directions are also discussed. As a digital tool for auxiliary diagnosis and treatment, orbital FEA will progressively unlock its potential for diagnosing and treating orbital diseases alongside technological advancements.

The extraction algorithm of target characteristics resonance set at the high-frequency band plays a significant role in defense applications like early warning. The paper proposes a new method to extract the characteristic resonance set of radar targets in the resonance frequency region using an autoregressive moving average model optimized by root mean square propagation particle swarm optimization. Considering that the total scattering response in the resonant region consists of early-time and late-time responses, the autoregressive moving average model approximate the total scattering responses to avoid errors caused by intercepting the late-time response. Further, the paper investigated the impact of the swarm optimization algorithm on the accuracy of moving average model parameters when obtaining the resonance set at different target aspects. The extracted characteristic resonance results within a range of azimuth directions through an aircraft target paradigm indicate that the new method is more convenient and precise than the matrix beam prediction method.

Controllable engineering of thin lithium (Li) metal is essential for increasing the energy density of solid-state batteries and clarifying the interfacial evolution mechanisms of a lithium metal negative electrode. However, fabricating a thin lithium electrode faces significant challenges due to the fragility and high viscosity of Li metal. Herein, through facile treatment of Ta-doped Li 7 La 3 Zr 2 O 12 (LLZTO) with trifluoromethanesulfonic acid, its surface Li 2 CO 3 species is converted into a lithiophilic layer with LiCF 3 SO 3 and LiF components. It enables the thickness control of Li metal negative electrodes, ranging from 0.78 μm to 30 μm. Quasi-solid-state lithium-metal battery with an optimized 7.54 μm-thick lithium metal negative electrode, a commercial LiNi 0.83 Co 0.11 Mn 0.06 O 2 positive electrode, and a negative/positive electrode capacity ratio of 1.1 shows a 500 cycles lifespan with a final discharge specific capacity of 99 mAh g -1 at 2.35 mA cm -2 and 25 °C. Through multi-scale characterizations of the thin lithium negative electrode, we clarify the multi-dimensional compositional evolution and failure mechanisms of lithium-deficient and -rich regions (0.78 μm and 7.54 μm), on its surface, inside it, or at the Li/LLZTO interface., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Electrochemical synthesis of hydrogen peroxide (H 2 O 2 ) via the two-electron oxygen reduction reaction (2e - -ORR) provides an alternative method to the energy-intensive anthraquinone method. Metal macrocycles with precise coordination are widely used for 2e - -ORR electrocatalysis, but they have to be commonly loaded on conductive substrates, thus exposing a large number of 2e - -ORR-inactive sites that result in poor H 2 O 2 production rate and efficiency. Herein, guided by first-principle predictions, a substrate-free and two-dimensional conductive metal-organic framework (Ni-TCPP(Co)), composed of CoN 4 sites in porphine(Co) centers and Ni 2 O 8 nodes, is designed as a multi-site catalyst for H 2 O 2 electrosynthesis. The approperiate distance between the CoN 4 and Ni 2 O 8 sites in Ni-TCPP(Co) weakens the electron transfer between them, thus ensuring their inherent activities and creating high-density active sites. Meanwhile, the intrinsic electronic conductivity and porosity of Ni-TCPP(Co) further facilitate rapid reaction kinetics. Therefore, outstanding 2e - -ORR electrocatalytic performance has been achieved in both alkaline and neutral electrolytes (>90 %/85 % H 2 O 2 selectivity within 0-0.8 V vs. RHE and >18.2/18.0 mol g -1  h -1 H 2 O 2 yield under alkaline/neutral conditions), with confirmed feasibility for water purification and disinfection applications. This strategy thus provides a new avenue for designing catalysts with precise coordination and high-density active sites, promoting high-efficiency electrosynthesis of H 2 O 2 and beyond., (© 2024 Wiley-VCH GmbH.)

The intrinsic reversibility of dynamic covalent bonding, such as the furan-maleimide Diels-Alder (DA) cycloaddition reactions, enables reprocessable, self-healing polymer materials that can be reconfigured via the mechanism of solid-state plasticity. In this work, the temperature-dependent exchange rates of stereochemically distinct endo and exo DA bonds are leveraged to achieve tunable, temperature- and stress-activated shape morphing in Diels-Alder polymer (DAP) networks. Through thermal annealing, ≈35% of endo DA isomers are converted in neat DAP networks to the thermodynamically favored exo form, achieving ≈97% exo after complete annealing at 60 °C. This conversion results in a ≈1.7 fold increase in elastic modulus, from 1.7 to 3.0 MPa, and significantly alters the stress relaxation and shape recovery behavior. Spatially resolved annealing, is further showcased enabling the precise control of spatial distributions of endo and exo DA bonds across planar geometries. The locally distinct concentrations of endo/exo isomers, achieved by temperature-induced conversion of endo DA isomers to the thermodynamically stable exo DA isomers, gave rise to the spatial distributions of stress relaxation rates and elastic strain recovery mismatch to enable controlled stereochemical shape morphing. This approach provides a simplified, thermally driven method for shape morphing, with potential applications in soft robotics and flexible electronics., (© 2024 Wiley‐VCH GmbH.)

Electroencephalography (EEG) microstates are canonical voltage topographies that reflect the temporal dynamics of brain networks on a millisecond time scale. Abnormalities in broadband microstate parameters have been observed in subjects with psychiatric symptoms, indicating their potential as clinical biomarkers. Considering distinct information provided by specific frequency bands of EEG, we hypothesized that microstates in decomposed frequency bands could provide a more detailed depiction of the underlying neuropathological mechanism. In this study, with a large open access resting-state dataset (n = 203), we examined the properties of frequency-specific microstates and their relationship with anxiety and depression symptoms. We conducted clustering on EEG topographies in decomposed frequency bands (delta, theta, alpha and beta), and determined the number of clusters with a meta-criterion. Microstate parameters, including global explained variance (GEV), duration, coverage, occurrence and transition probability, were calculated for eyes-open and eyes-closed states, respectively. Their ability to predict the severity of depression and anxiety symptoms were systematically identified by correlation, regression and classification analyses. Distinct microstate patterns were observed across different frequency bands. Microstate parameters in the alpha band held the best predictive power for emotional symptoms. Microstates B (GEV, coverage) and parieto-central maximum microstate E (coverage, occurrence, transitions from B to E) in the alpha band exhibited significant correlations with depression and anxiety, respectively. Microstate parameters of the alpha band achieved predictive R-square of 0.100 for anxiety scores, which is much higher than those of broadband (R-square = -0.026, p < 0.01). Similar results were found in classification of participants with high and low anxiety symptom scores (68% accuracy in alpha vs. 52% in broadband). These results suggested the value of frequency-specific microstates in predicting emotional symptoms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Daptomycin (DAP), a novel cyclic lipopeptide antibiotic produced by Streptomyces roseosporus, is clinically important for treatment of infections caused by multidrug-resistant Gram-positive pathogens, but the low yield hampers its large-scale industrial production. Here, we describe a combination metabolic engineering strategy for constructing a DAP high-yielding strain. Initially, we enhanced aspartate (Asp) precursor supply in S. roseosporus wild-type (WT) strain by separately inhibiting Asp degradation and competitive pathway genes using CRISPRi and overexpressing Asp synthetic pathway genes using strong promoter kasOp*. The resulting strains all showed increased DAP titre. Combined inhibition of acsA4, pta, pyrB, and pyrC increased DAP titre to 167.4 μg/mL (73.5% higher than WT value). Co-overexpression of aspC, gdhA, ppc, and ecaA led to DAP titre 168 μg/mL (75.7% higher than WT value). Concurrently, we constructed a chassis strain favourable for DAP production by abolishing by-product production (i.e., deleting a 21.1 kb region of the red pigment biosynthetic gene cluster (BGC)) and engineering the DAP BGC (i.e., replacing its native dptEp with kasOp*). Titre for the resulting chassis strain reached 185.8 μg/mL. Application of our Asp precursor supply strategies to the chassis strain further increased DAP titre to 302 μg/mL (2.1-fold higher than WT value). Subsequently, we cloned the engineered DAP BGC and duplicated it in the chassis strain, leading to DAP titre 274.6 μg/mL. The above strategies, in combination, resulted in maximal DAP titre 350.7 μg/mL (2.6-fold higher than WT value), representing the highest reported DAP titre in shake-flask fermentation. These findings provide an efficient combination strategy for increasing DAP production and can also be readily applied in the overproduction of other Asp-related antibiotics., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort.

Pathogens constantly evolve and can develop mutations that evade host immunity and treatment. Addressing these escape mechanisms requires targeting evolutionarily conserved vulnerabilities, as mutations in these regions often impose fitness costs. We introduce adaptive multi-epitope targeting with enhanced avidity (AMETA), a modular and multivalent nanobody platform that conjugates potent bispecific nanobodies to a human immunoglobulin M (IgM) scaffold. AMETA can display 20+ nanobodies, enabling superior avidity binding to multiple conserved and neutralizing epitopes. By leveraging multi-epitope SARS-CoV-2 nanobodies and structure-guided design, AMETA constructs exponentially enhance antiviral potency, surpassing monomeric nanobodies by over a million-fold. These constructs demonstrate ultrapotent, broad, and durable efficacy against pathogenic sarbecoviruses, including Omicron sublineages, with robust preclinical results. Structural analysis through cryoelectron microscopy and modeling has uncovered multiple antiviral mechanisms within a single construct. At picomolar to nanomolar concentrations, AMETA efficiently induces inter-spike and inter-virus cross-linking, promoting spike post-fusion and striking viral disarmament. AMETA's modularity enables rapid, cost-effective production and adaptation to evolving pathogens., Competing Interests: Declaration of interests Y.X. and Y.S. are co-inventors on a provisional patent of AMETA technology filed by Icahn School of Medicine at Mount Sinai. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories, and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer, and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and AstraZeneca. A.G.-S. is an inventor of patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. Y.X. and Y.S. are co-inventors on a patent of Nbs filed by Univ. of Pittsburgh. Y.S. is a co-founder of Antenna Biotech Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The performance of detectors is key for a PET scanner to achieve high spatial resolution and high sensitivity. This work aims to develop flood histogram generating algorithms to reduce the edge effect and improve the crystal identification of a PET detector consisting of two optically coupled pixelated scintillator detectors., Methods: The PET detector consists of two optically coupled detectors, each consisting of a 23×23 LYSO crystal array with a crystal size of 1.0×1.0×20 mm 3 read out by an 8×8 SiPM array with a pixel size of 3.0×3.0 mm 2 . The SiPM array is read out with a resistor network circuit to obtain four position encoding energy signals. A novel center of gravity (COG) positioning algorithm using six signals from the two detectors was proposed and compared to the traditional COG algorithms using either four or eight signals from the detectors. The raised-to-the-power (RTP) method was applied to the three COG algorithms for the PET detector. Different powers of the RTP from 1.0 to 2.5 were evaluated., Results: The proposed COG algorithm significantly improves the crystal identification at the junction of the two detectors as compared to the COG algorithm using four signals of each detector, and improves the crystal identification at the center of the two detectors as compared to the COG algorithm using eight signals from both detectors. The RTP method significantly improves the overall flood histogram qualities of the two COG algorithms using either eight or six signals from the two detectors, and the two COG algorithm provide similar flood histogram quality when a power of 1.5 is used., Conclusion: The novel positioning algorithms reduce the edge effect and improve the flood histogram quality for a PET detector consisting of two optically coupled detectors, each consisting of a pixelated scintillator crystal array and a SiPM array with highly multiplexed four signal readout. The positioning algorithms can be used in a PET scanner to improve the spatial resolution and sensitivity., (© 2024 American Association of Physicists in Medicine.)

Objective: In ophthalmic surgery, different materials and fixation methods are employed for bone flap repositioning after lateral orbitotomy approach (LOA), yet there is no unified standard. This study aims to investigate the impact of different fixation strategies on orbital stability through Finite Element Analysis (FEA) simulations of the biomechanical environment for orbital rim fixation in LOA., Methods: A Finite Element Model (FEM) was established and validated to simulate the mechanical responses under various loads in conventional lateral orbitotomy approach (CLOA) and deep lateral orbital decompression (DLOD) using single titanium plate, double titanium plates, and double absorbable plates fixation methods. The simulations were then validated against clinical cases., Results: Under similar conditions, the maximum equivalent stress (MES) on titanium alloy fixations was greater than that on absorbable plate materials. Both under static and physiological conditions, all FEM groups ensured structural stability of the system, with material stresses remaining within safe ranges. Compared to CLOA, DLOD, which involves the removal of the lateral orbital wall, altered stress conduction, resulting in an increase of MES and maximum total deformation (MTD) by 1.96 and 2.62 times, respectively. Under a horizontal load of 50 N, the MES in FEM/DLOD exceeded the material's own strength, with an increase in MES and MTD by 3.18 and 6.64 times, respectively, compared to FEM/CLOA. Under a vertical force of 50 N, the MES sustained by each FEM was within safe limits. Bone flap rotation angles remained minimally varied across scenarios. During follow-up, the 12 patients validated in this study did not experience complications related to the internal fixation devices., Conclusion: Under static or physiological conditions, various fixation methods can effectively maintain stability at the orbitotomy site, and absorbable materials, with their smoother stress transmission properties, are more suited for application in CLOA. Among titanium plate fixations, single titanium plates can better withstand vertical stress, while double titanium plates are more capable of handling horizontal stress. Given the change in the orbital mechanical behavior due to DLOD, enhanced fixation strength should be considered for bone flap repositioning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Zn ion batteries (ZIBs) are promising for large-scale energy storage but their practical application is plagued by inhomogeneous Zn deposition. Despite much effort, the harm of simultaneous hydrogen evolution reaction (HER) during plating to Zn deposition, has not received sufficient studies. Herein, Sn-modified Cu nanowires (Sn@CuNWs) with Sn-Cu core-shell nanostructure to achieve uniform Zn deposition by zinc affinity-HER tendency trade-off are fabricated. Confirmed by both theoretical calculation and practical characterization, the nanowires with high zinc affinity and large deposition sites facilitate Zn deposition, while the enlarged HER tendency harmful to Zn plating is inhibited by Sn nanoshell. Therefore, the Zn deposited Sn@CuNWs anode delivers a long lifespan of 800 h at 5 mA cm -2 , and the full cell exhibits a high capacity of 294.4 mAh g -1 at 5 A g -1 and a high capacity retention of 97.8% after 2500 cycles. This work reveals the importance of HER regulation for reversible Zn deposition, which should be noticed in further research., (© 2024 Wiley‐VCH GmbH.)

Background: The correlation between heading date and flowering time significantly regulates grain filling and seed formation in barley and other crops, ultimately determining crop productivity. In this study, the transcriptome, hormone content detection, and metabolome analysis were performed systematically to analyze the regulatory mechanism of heading time in highland barley under different light conditions. The heading date of D18 (winter highland barley variety, Dongqing18) was later than that of K13 (vernal highland barley variety) under normal growth conditions or long-day (LD) treatment, while this situation will reverse with short-day (SD) treatment., Results: The circadian rhythm plant, plant hormone signaling transduction, starch and sucrose metabolism, and photosynthesis-related pathways are significantly enriched in barley under SD and LD to influence heading time. In the plant circadian rhythm pathway, the key genes GI (Gigantea), PRR (Pesudoresponseregulator), FKF1 (Flavin-binding kelch pepeat F-Box 1), and FT (Flowering locus T) are identified as highly expressed in D18SD3 and K13SD2, while they are significantly down-regulated in K13SD3. These genes play an important role in regulating the heading date of D18 earlier than that of K13 under SD conditions. In photosynthesis-related pathways, a-b binding protein and RBS were highly expressed in K13LD3, while NADP-dependent malic enzyme, phosphoenolpyruvate carboxylase, fructose-bisphosphate aldolase, and triosephosphate isomerase were significantly expressed in D18SD3. In the starch and sucrose metabolism pathway, 41 DEGs (differentially expressed genes) and related metabolites were identified as highly expressed and accumulated in D18SD3. The DEGs SAUR (Small auxin-up RNA), ARF (Auxin response factor), TIR1 (Transport inhibitor response 1), EIN3 (Ethylene-insensitive 3), ERS1 (Ethylene receptor gene), and JAZ1 (Jasmonate ZIM-domain) in the plant hormone pathway were significantly up-regulated in D18SD3. Compared with D18LD3, the content of N6-isopentenyladenine, indole-3-carboxylic acid, 1-aminocyclopropanecarboxylic acid, trans-zeatin, indole-3-carboxaldehyde, 1-O-indol-3-ylacetylglucose, and salicylic acid in D18SD3 also increased. The expression levels of vernalization genes (HvVRN1, HvVRN2, and HvVRN3), photoperiod genes (PPD), and PPDK (Pyruvate phosphate dikinase) that affect photosynthetic efficiency in barley are also analyzed, which play important regulatory roles in barley heading date. The WGCNA analysis of the metabolome data and circadian regulatory genes identified the key metabolites and candidate genes to regulate the heading time of barley in response to the photoperiod., Conclusion: These studies will provide a reference for the regulation mechanism of flowering and the heading date of highland barley., (© 2024. The Author(s).)

Ovarian cancer (OC) is one of the most common malignancies and a leading cause of death among women worldwide. The ubiquitin pathway plays an important role in OC development. Using the single nucleotide polymorphism data obtained using the prevalence and dominance strategies, four ubiquitin marker genes were identified according to their expression levels: BARD1, BRCA2, FANCA, and BRCA1. Based on these four genes, a consensus clustering of OC expression data was performed. The significant differences in the survival analysis, ESTIMATE, and CIBERSORT results among the clusters indicated the pivotal role of these four genes in OC development. Of the ubiquitin-representative genes in each cluster, two ubiquitin genes, TOP2A and MYLIP , were identified in the survival risk model after univariate survival, Least Absolute Shrinkage and Selection Operator regression, and multivariate survival analyses. The reliability and robustness of both the training and validation data were confirmed by comparing the significant survival difference between high- and low-risk patients. We further explored the association between our risk model and clinical outcomes as well as predicted potentially interacting drugs. The co-expression network showed clear interactions among the four marker genes and two model genes and between high- and low-risk differentially expressed genes. Significantly enriched genes were found in pathways associated with ion channels, channel activity, and neuroactive ligand-receptor interactions. Therefore, suggesting the involvement of ubiquitin genes in the survival and development of OC through neurohumoral regulation. Our results will provide valuable reference or supplementary information for studies investigating OC diagnosis and therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: A local microneedle patch loaded with 5-aminolevulinic acid (ALA) was constructed to improve the efficiency of ALA photodynamic treatment of oral leukoplakia, reduce local photosensitivity reactions, and promote the healing of lesions., Methods: The microneedle patch loaded with ALA was constructed with the hyaluronic acid (HA) solution (ALA-HAMN), and its morphology, strength, mucosal penetration, and biocompatibility were tested., Results: In vivo safety and permeability tests confirmed that ALA-HAMN had good biocompatibility and could penetrate the mucosal barrier and quickly dissolve and release ALA for in situ transdermal administration. The 4-nitroquinoline oxide (NQO) rat model experiment showed that ALA-HAMN can significantly improve photodynamic therapy (PDT) efficiency and has no damage to mucosal tissue compared with the commonly used ALA cotton ball dressing., Conclusions: The ALA-loaded microneedle patch was successfully constructed for the photodynamic treatment of oral leukoplakia, and the photodynamic efficiency and comfort of oral leukoplakia were improved, which provided an effective delivery mode to improve clinical ALA-PDT treatment of oral leukoplakia (OLK)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Designing non-noble metal single-atom catalysts (M-SACs) for two-electron oxygen reduction reaction (2e-ORR) is attractive for the hydrogen peroxide (H 2 O 2 ) electrosynthesis, in which the coordination configuration of the M-SACs essentially affects the reaction activity and product selectivity. Though extensively investigated, a generalized coordination engineering strategy has not yet been proposed, which fundamentally hinders the rational design of M-SACs with optimized catalytic capabilities. Herein, a generalized coordination engineering strategy is proposed for M-SACs toward H 2 O 2 electrosynthesis via introducing heteroatoms (e.g., oxygen or sulfur atoms) with higher or lower electronegativity than nitrogen atoms into the first sphere of metal-N 4 system to tailor their electronic structure and adjust the adsorption strength for * OOH intermediates, respectively, thus optimizing their electrocatalytic capability for 2e-ORR. Specifically, the (O, N)-coordinated Co SAC (Co-N 3 O) and (S, N)-coordinated Ni SAC (Ni-N 3 S) are precisely synthesized, and both present superior 2e-ORR activity (E onset : ≈0.80 V versus RHE) and selectivity (≈90%) in alkaline conditions compared with conventional Co-N 4 and Ni-N 4 sites. The high H 2 O 2 yield rates of 14.2 and 17.5 moL g -1  h -1 and long-term stability over 12 h are respectively achieved for Co-N 3 O and Ni-N 3 S. Such favorable 2e-ORR pathway of the catalysts is also theoretically confirmed by the kinetics simulations., (© 2024 Wiley‐VCH GmbH.)

This study aimed to explore the influence of excess iodine on the articular cartilage and epiphyseal growth plate in rats. Wistar rats (n = 200) were randomly divided into five groups with 40 rats in each: normal iodine (NI), 5-fold high iodine group (5HI), 10-fold high iodine group (10HI), 50-fold high iodine group (50HI), and 100-fold high iodine group (100HI). The rats were executed in 6 and 12 months. 24-h urinary iodine concentration (UIC) was monitored by arsenic-cerium catalytic spectrophotometry. The chemiluminescence method was used to determine the thyroid function. The pathological changes in the epiphyseal plate, articular cartilage, and thickness of the epiphyseal plate were observed. The mRNA expression of collagen II (ColII), collagen X, matrix metalloproteinase-13 (MMP-13), and fibroblast growth factor receptor 1 in articular chondrocytes was detected by RT-PCR. 24-h UIC increased as iodine intake increased. In the 12th month, there was a significant increase in serum sTSH and a decrease in serum FT 4 in HI groups, compared to the NI group. There was a decrease in the number of proliferating cells in the epiphyseal plate and an increase in the number of mast cell layers. The chondrocytes appeared disorganized, and the tidal lines were disturbed or even broken. Growth plate thickness decreased with increasing iodine intake. Compared with the NI group, ColII and MMP-13 mRNA expression in chondrocytes in all HI groups significantly increased. Chronic iodine overdose increases the risk of hypothyroidism. Chronic iodine overdose leads to abnormal morphology of epiphyseal growth plates and articular cartilage, increasing the risk of osteoarthritis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Magnolia wufengensis , a newly discovered ornamental species in the Magnoliaceae family, is susceptible to salinity. Moreover, Ca 2+ is an essential element for plant growth and is receiving increasing attention for its ability to mitigate the negative effects of environmental stress on plants. In the present study, we investigated the effect of Ca 2+ on the growth and transcriptome of M. wufengensis under salt stress. The treatments used here were as follows: control, NaCl (150 mmol/L), CaCl 2 (5 mmol/L), and NaCl (150 mmol/L) + CaCl 2 (5 mmol/L). After a 60-day treatment period, plant growth indices were determined, and leaves were collected for physiological analysis and transcriptome investigation. The combined application of NaCl and CaCl 2 alleviated phenotypic damage and restored seedling growth. Moreover, RNA sequencing data revealed that in the Na vs. control group and the NaCa vs. Na group, there were 968 and 2632 differentially expressed genes, respectively, which were both primarily enriched in secondary metabolism, glutathione metabolism, signaling hormone metabolism, glucose metabolism, and amino acid metabolism. These pathways were analyzed to screen key genes: the adenosine triphosphate (ATP)-binding cassette efflux transporter G1 (ABCG1) genes, which are related to transmembrane transport; the calmodulin genes, which are related to signal transmission; and the glutathione S-transferase (GST), glutathione peroxidase (GPX), and peroxidase (POD) genes related to antioxidant enzymes. Lastly, we constructed a hypothesis model of Ca 2+ -enhanced salt tolerance in M. wufengensis . This study reveals the potential mechanisms by which Ca 2+ enhances the salt tolerance of M. wufengensis and provides a theoretical reference for its cultivation in saline areas.

Spinal cord injury is a serious traumatic nervous system disorder characterized by extensive neuronal apoptosis. Oxidative stress, a key factor in neuronal apoptosis, leads to the accumulation of reactive oxygen species, making mitochondrial quality control within cells crucial. Previous studies have demonstrated zinc's anti-inflammatory and anti-apoptotic properties in protecting mitochondria during spinal cord injury treatment, yet the precise mechanisms remain elusive. Single-cell sequencing analysis has identified Lgals3 and Bax as core genes in apoptosis. This study aimed to investigate whether zinc ions protect intracellular mitochondria by inhibiting the apoptotic proteins Lgals3 and Bax. We elucidated zinc ions' key role in mitigating mitochondrial quality control dysfunction triggered by oxidative stress and confirmed this was achieved by targeting the Lgals3-Bax pathway. Zinc's inhibitory effect on this pathway not only preserved mitochondrial integrity but also significantly reduced PANoptosis after spinal cord injury. Under oxidative stress, zinc ion regulation of mitochondrial quality control reveals an organelle-targeted therapeutic strategy, offering a novel approach for more precise treatment of spinal cord injury., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Herein, we present a one-pot method for the direct cross-coupling of aryl diazonium salts and aryl bromides in an economical way that avoids the use of sensitive organometallic reagents. The reaction is accomplished with the assistance of nickel catalysts, ligands, magnesium turnings, lithium chloride, and triethylamine, avoiding the use of pre-activated organometallic reagents.

Background: Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) stand as pivotal diagnostic tools for brain disorders, offering the potential for mutually enriching disease diagnostic perspectives. However, the costs associated with PET scans and the inherent radioactivity have limited the widespread application of PET. Furthermore, it is noteworthy to highlight the promising potential of high-field and ultra-high-field neuroimaging in cognitive neuroscience research and clinical practice. With the enhancement of MRI resolution, a related question arises: can high-resolution MRI improve the quality of PET images?, Purpose: This study aims to enhance the quality of synthesized PET images by leveraging the superior resolution capabilities provided by high-field and ultra-high-field MRI., Methods: From a statistical perspective, the joint probability distribution is considered the most direct and fundamental approach for representing the correlation between PET and MRI. In this study, we proposed a novel model, the joint diffusion attention model, namely, the joint diffusion attention model (JDAM), which primarily focuses on learning information about the joint probability distribution. JDAM consists of two primary processes: the diffusion process and the sampling process. During the diffusion process, PET gradually transforms into a Gaussian noise distribution by adding Gaussian noise, while MRI remains fixed. The central objective of the diffusion process is to learn the gradient of the logarithm of the joint probability distribution between MRI and noise PET. The sampling process operates as a predictor-corrector. The predictor initiates a reverse diffusion process, and the corrector applies Langevin dynamics., Results: Experimental results from the publicly available Alzheimer's Disease Neuroimaging Initiative dataset highlight the effectiveness of the proposed model compared to state-of-the-art (SOTA) models such as Pix2pix and CycleGAN. Significantly, synthetic PET images guided by ultra-high-field MRI exhibit marked improvements in signal-to-noise characteristics when contrasted with those generated from high-field MRI data. These results have been endorsed by medical experts, who consider the PET images synthesized through JDAM to possess scientific merit. This endorsement is based on their symmetrical features and precise representation of regions displaying hypometabolism, a hallmark of Alzheimer's disease., Conclusions: This study establishes the feasibility of generating PET images from MRI. Synthesis of PET by JDAM significantly enhances image quality compared to SOTA models., (© 2024 American Association of Physicists in Medicine.)

Background: The impact of transcatheter closure of coronary artery fistula (CAF) and residual shunt after occlusion on improving blood flow in the donor vessel remains uncertain., Objectives: To evaluate the functional impact on the donor vessel following CAFs closure using QFR (Quantitative Flow Ratio) analysis., Methods: A total of 46 patients with 48 CAFs who underwent transcatheter closure at Shanghai Chest Hospital and Shuguang Hospital between March 2015 and August 2023 were included in the review. The clinical, angiographic details, and QFR data were subjected to analysis. The size of the fistulae was defined according to the ratio between the diameters of the fistulae and the largest diameter of the coronary vessel not feeding the coronary fistula., Results: Among 48 CAFs, the average diameter of the fistulae ostium was 3.19 ± 1.04 mm, while the mean diameter of the donor vessel segment following fistulae was 3.45 ± 1.01 mm. The mean QFR value of the donor vessels with medium CAFs was found to be significantly lower than those with small CAFs (0.93 ± 0.10 vs. 0.98 ± 0.03; p  < 0.05). Furthermore, the mean QFR value of donor vessels with medium CAFs was observed to be significantly improved after occlusion (0.99 ± 0.01 vs. 0.93 ± 0.10; p  = 0.01). However, there was no statistical difference in the mean QFR value of donor vessels with small CAFs before and after occlusion (0.98 ± 0.03 vs. 0.98 ± 0.02; p  > 0.05). Moreover, the changes in QFR were more pronounced in donor vessels with medium CAFs compared to those with small CAFs after occlusion (0.06 ± 0.10 vs. 0.005 ± 0.012; p  = 0.01). There is no statistical difference in the mean QFR variation and QFR variation rate between donor vessels with CAFs that occurred residual shunt and those without residual shunt after occlusion ( p  > 0.05)., Conclusions: The presence of medium CAFs has a significant impact on the blood flow of the donor vessel, as compared to small CAFs, and may benefit from occlusion. A small residual shunt has no significant impact on the effectiveness of CAFs occlusion in enhancing donor blood flow., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Sang, Ji, Tong, Shen, Wang and He.)

Background: Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined., Objective: To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow., Design: Single-center cross-sectional cohort study., Methods: Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH., Results: A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all P -values <0.05. After adjusting for other covariates, forward mean flow at ipsilateral infarction MCA is still associated with severe WMH independently, OR = 0.537, 95% CI (0.294, 0.981), P = 0.043., Conclusion: Intracranial artery stenosis patients with coexisting severe WMH suffer from significantly decreased flow, which could explain the poor clinical outcome in this population, and also provide some insight into recanalization therapy in the future., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Advancing the high-voltage stability of the O3-type layered cathodes for sodium-ion batteries is critical to boost their progress in energy storage applications. However, this type of cathode often suffers from intricate phase transition and structural degradation at high voltages (i.e., >4.0 V vs Na + /Na), resulting in rapid capacity decay. Here, we present a Li/Ti cosubstitution strategy to modify the electronic configuration of oxygen elements in the O3-type layered oxide cathode. This deliberate modulation simultaneously mitigates the phase transitions and counteracts the weakening of the shielding effect resulting from the extraction of sodium ions, thus enhancing the electrostatic bonding within the TM layer and inducing and optimizing the O3-OP2 phase transition occurring in the voltage range of 2.0-4.3 V. Consequently, the cosubstituted NaLi 1/9 Ni 1/3 Mn 4/9 Ti 1/9 O 2 exhibits an astounding capacity of 161.2 mAh g -1 in the voltage range of 2.0-4.3 V at 1C, and stable cycling up to 100 cycles has been achieved. This work shows the impact mechanism of element substitution on interlayer forces and phase transitions, providing a crucial reference for the optimization of O3-type materials.

Background: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis)., Results: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal., Conclusions: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem., (© 2024. The Author(s).)

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly‑oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC 50 values ranging from 24.83 to 45.46 μM, while the IC 50 values of the positive control adriamycin was ranging from 1.11 to 1.44 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Open science skills are increasingly important for a career in ecology and evolutionary biology (EEB) as efforts to make data and analyses publicly available continue to become more commonplace. While learning core concepts in EEB, students are also expected to gain skills in conducting open science to prepare for future careers. Core open science skills like programming, data sharing, and practices that promote reproducibility can be taught to undergraduate students alongside core concepts in EEB. Yet, these skills are not always taught in biology undergraduate programs, and a major challenge in developing open science skills and learning EEB concepts simultaneously is the high cognitive load associated with learning multiple disparate concepts at the same time. One solution is to provide students with easily digestible, scaffolded, pre-formatted code in the form of vignettes and interactive tutorials. Here, we present six open source teaching tutorials for undergraduate students in EEB. These tutorials teach fundamental ecological concepts, data literacy, programming (using R software), and analysis skills using publicly available datasets while introducing students to open science concepts and tools. Spanning a variety of EEB topics and skill levels, these tutorials serve as examples and resources for educators to integrate open science tools, programming, and data literacy into teaching EEB at the undergraduate level., Competing Interests: The authors declare that there are no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC 50  = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC 50  = 0.51 ± 0.20 μM, EC 50  = 2.24 ± 0.43 μM, CC 50  = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the Hydrodynamic-Injection (HDI) mouse model. Therefore, compound 26f could be considered as a promising candidate drug for further development of novel HBV CAMs with the desired potency and safety., Competing Interests: Declaration of competing interest The authors declared that there were no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.

The availability of an alternative and efficient genetic editing technology is critical for fundamental research and strain improvement engineering of Streptomyces species, which are prolific producers of complex secondary metabolites with significant pharmaceutical activities. The mobile group II introns are retrotransposons that employ activities of catalytic intron RNAs and intron-encoded reverse transcriptase to precisely insert into DNA target sites through a mechanism known as retrohoming. We here developed a group II intron-based gene editing tool to achieve precise chromosomal gene insertion in Streptomyces. Moreover, by repressing the potential competition of RecA-dependent homologous recombination, we enhanced site-specific insertion efficiency of this tool to 2.38%. Subsequently, we demonstrated the application of this tool by screening and characterizing the secondary metabolite biosynthetic gene cluster (BGC) responsible for synthesizing the red pigment in Streptomyces roseosporus. Accompanied with identifying and inactivating this BGC, we observed that the impair of this cluster promoted cell growth and daptomycin production. Additionally, we applied this tool to activate silent jadomycin BGC in Streptomyces venezuelae. Overall, this work demonstrates the potential of this method as an alternative tool for genetic engineering and cryptic natural product mining in Streptomyces species., (© 2024 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd.)

Background: To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model., Methods: We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA)., Results: We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819-0.928) and 0.772 (95% CI: 0.699-0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P < 0.05). A combined nomogram was constructed from these factors, and AUC reached 0.934 (95% CI: 0.896-0.972). DCA demonstrated that the clinical benefits brought by the nomogram for patients across an extensive range were greater than those of other individual models., Conclusions: By combining CT radiomics, hematological factors, and clinicopathological characteristics before treatment, we developed a nomogram model that effectively predicted whether ESCC patients would achieve pCR after nICT, thus identifying patients who are sensitive to nICT and assisting in clinical treatment decision-making., (© 2024. The Author(s).)

Background: Although iodine modulates bone metabolism in the treatment of thyroid disease, the effect of iodine intake on bone metabolism remains less known., Objective: This study evaluated the effect of excess iodine intake in rats on bone reconstruction in the 6th and 12th month of intervention., Method: Rats were treated with different doses of iodinated water: the normal group (NI, 6.15 μg/d), 5-fold high iodine group (5HI, 30.75 μg/d), 10-fold high iodine group (10HI, 61.5 μg/d), 50-fold high iodine group (50HI, 307.5 μg/d), and 100-fold high iodine group (100HI, 615 μg/d). Thyroid hormone concentrations were determined by a chemiluminescent immunoassay. Morphometry and microstructure of bone trabecula were observed by hematoxylin and eosin staining and microcomputed tomography, respectively. Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining were performed to evaluate the activity of osteoblasts and osteoclasts, respectively., Results: The 24-h urine iodine concentration increased with iodine intake. The rats in the HI groups had higher serum thyroid-stimulating hormone and decreased serum free thyroxine concentrations in the 12th month than the NI group (all P < 0.05). The percentage of the trabecular bone area and osteoblast perimeter in the 100HI group were significantly lower than those in the NI group (P < 0.05). Increased structure model index was observed in the 50HI and 100HI groups compared with the NI group in the 6th month and increased trabecular separation in the 12th month (all P < 0.05). ALP and TRAP staining revealed osteoblastic bone formation was reduced, and the number of TRAP+ multinucleated cells decreased with increasing iodine intake., Conclusions: Excess iodine intake may increase the risk of hypothyroidism in rats. Chronic excess iodine intake can lead to abnormal changes in skeletal structure, resulting in reduced activity of osteoblasts and osteoclasts, which inhibits the process of bone reconstruction and may lead to osteoporosis., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

This study aimed to assess the feasibility of utilizing a surgical guide, designed through digital medical technology, in lateral orbital decompression surgery. METHODS: In total, 18 patients with thyroid-associated ophthalmopathy (TAO), who underwent orbital balance decompression surgery at the Affiliated Eye Hospital of Nanchang University between September 2018 and August 2022, were included. Orbital CT scanning was performed on all patients with TAO, and Mimics 21.0 software was used to reconstruct a three-dimensional model of the orbit based on the CT data. The osteotomy guide plate for lateral orbital decompression surgery was designed using 3-matic 13.0 software, adhering to the criteria of surgical effectiveness and safety. The surgical positioning guide was designed using Geomagic Wrap 21.0. Once printed, the surgical guide was sterilized with low-temperature plasma and applied during surgery. Of the nine patients treated using a surgical navigation system, three cases experienced cerebrospinal fluid leakage complications during the procedure, and two exhibited inadequate bone removal along the lateral wall. In contrast, among the nine patients treated with surgical guides, no intraoperative cerebrospinal fluid leakage or evidence of insufficient lateral wall bone removal was observed, highlighting a statistically significant distinction between the two cohorts (p = 0.046). Postoperative improvements were notable in best-corrected visual acuity (BCVA) and exophthalmos for patients afflicted with extremely severe TAO. The surgical guide, designed with digital medical technology, has been shown to be an effective and secure auxiliary tool in lateral orbital decompression surgery. It not only aids in reducing the incidence of intraoperative complications, but also enhances the accuracy and safety of surgery. These improvements offer robust support for continued exploration in this field within clinical practice., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The objective of this study is to explore the pharmacokinetics, tissue distribution, and excretion patterns of GL-V9 and its glucuronide metabolite, 5-O-glucuronide GL-V9, following the administration of GL-V9 to Sprague-Dawley (SD) rats. In this research, we developed and validated rapid, sensitive, and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods for quantifying GL-V9 and 5-O-glucuronide GL-V9 in various biological samples, including SD rat plasma, tissue homogenate, bile, urine, and feces. Quantification of GL-V9 and 5-O-glucuronide GL-V9 in plasma, tissue homogenate, bile, urine, and feces was performed using the validated LC-MS/MS methods. The bioavailability of GL-V9 in SD rats ranged from 6.23% to 7.08%, and both GL-V9 and 5-O-glucuronide GL-V9 exhibited wide distribution and rapid elimination from tissues. The primary distribution tissues for GL-V9 and 5-O-glucuronide GL-V9 in rats were the duodenum, liver, and lung. GL-V9 was predominantly excreted in urine, while 5-O-glucuronide GL-V9 was primarily excreted in bile. GL-V9 exhibited easy absorption and rapid conversion to its glucuronide metabolite, 5-O-glucuronide GL-V9, following administration., (© 2024 John Wiley & Sons Ltd.)

Bitter melon fruit is susceptible to yellowing, softening, and rotting under room-temperature storage conditions, resulting in reduced commercial value. Nitric oxide (NO) is an important signaling molecule and plays a crucial role in regulating the fruit postharvest quality. In this study, we investigated the effects of NO treatment on changes in sensory and firmness of bitter melon fruit during postharvest storage. Moreover, transcriptomic, metabolomic, and proteomic analyses were performed to elucidate the regulatory mechanisms through which NO treatment delays the ripening and senescence of bitter melon fruit. Our results show that differentially expressed genes (DEGs) were involved in fruit texture ( CSLE , β-Gal , and PME ), plant hormone signal transduction ( ACS , JAR4 , and AUX28 ), and fruit flavor and aroma ( SUS2 , LOX , and GDH2 ). In addition, proteins differentially abundant were associated with fruit texture (PLY, PME, and PGA) and plant hormone signal transduction (PBL15, JAR1, and PYL9). Moreover, NO significantly increased the abundance of key enzymes involved in the phenylpropanoid biosynthetic pathway, thus enhancing the disease resistance and alleviating softening of bitter melon fruit. Finally, differential metabolites mainly included phenolic acids, terpenoids, and flavonoids. These results provide a theoretical basis for further studies on the physiological changes associated with postharvest ripening and senescence of bitter melon fruit., Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00110-y., Competing Interests: Conflict of interestThe authors declare that they have no competing commercial interests concerning this work., (© The Author(s) 2024.)

Two previously unreported lignans (1-2) and four undescribed [11]-chaetoglobosins (3-6) were obtained from the culture extract of an endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were determined by spectroscopic data analysis, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, the modified Mosher's method, and Mo 2 (OAc) 4 -induced electronic circular dichroism (ICD) experiments. Compounds 5 and 6 showed moderate cytotoxic effects against seven human cancer cell lines. Compounds 2-4 exhibited immunosuppressive activities on concanavalin A-induced T cell proliferation with IC 50 values of 3.7, 3.4, and 14.5 μM, and on lipopolysaccharide-induced B cell proliferation with IC 50 values of 4.1, 3.9, and 14.2 μM, respectively. Further investigation revealed that 2 and 3 induced apoptosis in activated T cells in a dose-dependent manner.

In this study, a novel series of diarylpyrimidine derivatives with Fsp 3 -enriched spirocycles were designed and synthesized to further explore the chemical space of the hydrophobic channel of the NNRTI-binding pocket. The biological evaluation results showed that most of the compounds displayed effective inhibitory potency against the HIV-1 wild-type strain, with EC 50 values ranging from micromolar to submicromolar levels. Among them, TT6 turned out to be the most effective inhibitor with an EC 50 value of 0.17 μM, demonstrating up to 47 times more active than that of reference drug 3TC (EC 50  = 8.01 μM). More encouragingly, TT6 was found to potently inhibit the HIV-1 mutant strain K103N with an EC 50 value of 0.69 μM, being about 6-fold more potent than 3TC (EC 50  = 3.68 μM) and NVP (EC 50  = 4.62 μM). Furthermore, TT6 exhibited the most potent inhibitory activity toward HIV-1 reverse transcriptase with an IC 50 value of 0.33 μM. Additionally, molecular simulation studies were conducted to investigate the binding modes between TT6 and NNRTI-binding pocket, which may provide valuable clues for the follow-up structural optimizations., (© 2024 John Wiley & Sons Ltd.)

With our continuous endeavors in seeking potent anti-HIV-1 agents, we reported here the discovery, biological characterization, and druggability evaluation of a class of nonnucleoside reverse transcriptase inhibitors. To fully explore the chemical space of the NNRTI-binding pocket, novel series of dihydrothiopyrano [3,2- d ]pyrimidines were developed by employing the structure-based design strategy. Most of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar levels. Among them, compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor, with EC 50 values ranging from 3.43 to 21.4 nmol/L. Especially, for the challenging double-mutants F227L + V106A and K103N + Y181C, 23h exhibited 2.3- to 14.5-fold more potent activity than the first-line drugs efavirenz and etravirine. Besides, the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and etravirine. The binding target of 23h was further confirmed to be HIV-1 reverse transcriptase. Molecular modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization campaign. Furthermore, no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for 23h . Most importantly, 23h was characterized by good pharmacokinetic properties and excellent safety in vivo . Collectively, 23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors.)

Ultra-narrow pulses serve as critical components in numerous applications. These pulses have ultra-fast leading edges that typically function as precision trigger signals to synchronize various instruments. Ultra-narrow pulses inherently exhibit an ultra-wide bandwidth, gaining significant attention in diverse electronic systems encompassing communications, radar imaging, electronic warfare, and others. Although several techniques have been explored for generating ultra-narrow pulses, field programmable gate arrays (FPGAs) offer a promising alternative in terms of flexibility and integration. This study introduces a scalable delay pulse synchronizer method with a resolution of 23 ps. A programmable, successive, narrow pulse sequence operating at a 1-GHz repetition frequency is implemented within a monolithic FPGA. The performance of the proposed method is evaluated using an existing board with a general commercial FPGA in the laboratory. This new method presents a convenient and efficient approach of achieving ultra-narrow pulse synchronization, being applicable across various fields., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Three new indole diketopiperazines, ochrolines A-C (1-3), along with three known compounds (4-6), were isolated and identified from the EtOAc extract of the solid fermentation of Bionectria ochroleuca SLJB-2. Notably, compound 1 featured a natural rarely-occurring caged skeleton with a 6/5/6/7 heterotetracyclic bridged ring system. The structures including absolute configurations of 1-3 were fully accomplished by extensive spectroscopic analyses, DFT GIAO 13 C NMR and electronic circular dichroism (ECD) calculations. The plausible biogenetic pathways of these new indole diketopiperazines were also proposed. Moreover, the cytotoxic activity screening revealed that compound 2 exhibited moderate inhibitory effect against A549 with inhibition rate of 57.44% at the concentration of 50 μM and compound 1 exhibited mild inhibitory activities against A549, Hela and MCF-7., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2023. Published by Elsevier B.V.)

The aim of this study was to estimate the association between blood urea nitrogen (BUN) and clinical prognosis in patients with COVID-19. A multicenter, retrospective study was conducted in adult patients with COVID-19 in 3 hospitals in Zhenjiang from January 2023 to May 2023. Patients were divided into survival and death group based on whether they survived at day 28. The demographic, comorbidities, and laboratory data were independently collected and analyzed, as well as clinical outcomes. Total 141 patients were enrolled and 23 (16.3%) died within 28 days. Patients who died within 28 days had a higher level of BUN compared with survivors. Bivariate logistic regression analysis showed that BUN was a risk factor for 28-day mortality in patients with COVID-19. ROC curve showed that BUN could predict 28-day mortality of COVID-19 patients (AUC = 0.796, 95%CI: 0.654-0.938, P < .001). When the cutoff value of BUN was 7.37 mmol/L, the sensitivity and specificity were 84.62% and 70.31%. Subgroup analysis demonstrated that hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality among COVID-19 patients. Patients with COVID-19 who died within 28 days had a higher level of BUN, and hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Formation of starch-polyphenol complexes by high pressure homogenization (HPH) is widely used to reduce starch digestibility and delay the postprandial glycemic response, thereby benefiting obesity and associated metabolic diseases. This study investigated the effect of complexation temperature on multi-scale structures, physicochemical and digestive properties of pea starch-gallic acid (PS-GA) complexes during HPH process, while also elucidating the corresponding molecular mechanism regulating in vitro digestibility. The results demonstrated that elevating complexation temperature from 30 °C to 100 °C promoted the interaction between PS and GA and reached a peak complex index of 9.22 % at 90 °C through non-covalent binding. The enhanced interaction led to the formation of ordered multi-scale structures within PS-GA complexes, characterized by larger particles that exhibited greater thermal stability and elastic properties. Consequently, the PS-GA complexes exhibited substantially reduced digestion rates with the content of resistant starch increased from 28.50 % to 38.26 %. The potential molecular mechanism underlying how complexation temperature regulated digestibility of PS-GA complexes might be attributed to the synergistic effect of the physical barriers from newly ordered structure and inhibitory effect of GA against digestive enzymes. Overall, our findings contribute to the advancement of current knowledge regarding starch-polyphenol interactions and promote the development of functional starches with low postprandial glycemic responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The aim of the study was to discuss the catastrophic consequences of inequitable vaccine distribution and analyze the main challenges to address it, helping to guide efforts to address inequities in vaccine coverage., Methods: All published papers written in English were searched through PubMed, Web of Science, and Google Scholar with the combination of relevant terms of COVID-19 vaccine inequity., Results: In this paper, we first outlined the scope of inequitable vaccine distribution and identify its truly catastrophic consequences. Next, from the perspectives of political will, free markets, and profit-driven enterprises based on patent and intellectual property protection, we analyzed in depth the root causes of why this phenomenon is so difficult to combat. In addition, some specific and crucial solutions that should be undertaken in the long term were also put forward in order to provide a useful reference for the authorities, stakeholders, and researchers involved in addressing this worldwide crisis and the next one., Conclusions: Achieving COVID-19 vaccine equity faces funding gaps, vaccine nationalism, and barriers to access to intellectual property and technology. Thus, the scope of global vaccine inequity is immense, and its repercussions will continue to be felt worldwide, especially among the world's most vulnerable residents, both adults and children. Beyond fundamental issues, the growing vaccine hesitancy and unreliable distribution in low-income countries must be addressed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Compared with traditional tedious organic solvent-assisted separation process in natural medicinal chemistry, cytomembrane (CM) fishing technique became a more appealing and greener choice for screening bioactive components from natural products. However, its large-scale practical value was greatly weakened by the easy fall-off of CMs from magnetic supports, rooted in the instability of common Fe 3 O 4 particles and their insufficient interaction with CMs. In this research, a new green biostable platform was developed for drug screening through the integration of hyperbranched quaternized hydrothermal magnetic carbon spheres (HQ-HMCSs) and CMs. The positive-charged HQ-HMCSs were constructed by chitosan-based hydrothermal carbonization onto Fe 3 O 4 nanospheres and subsequent aqueous hyperbranching quaternization with 1,4-butanediol diglycidyl ether and methylamine. The strong interaction between HQ-HMCSs and CMs was formed via electrostatic attraction of HQ-HMCSs to negative-charged CMs and covalent linkage derived from the epoxy-amine addition reactions. The chemically stable HMCSs and its integration with CMs contributed to dramatically higher stability and recyclability of bionic nanocomposites. With the fishing of osteoblast CMs integrated HQ-HMCSs, two novel potential anti-osteoporosis compounds, narcissoside and beta-ionone, were discovered from Hippophae rhamnoides L. Enhanced osteoblast proliferation, alkaline phosphatase, and mineralization levels proved their positive osteogenesis effects. Preliminary pharmacological investigation demonstrated their potential action on membrane proteins of estrogen receptor alpha and insulin-like growth factor 1. Furthermore, beta-ionone showed apparent therapeutic effects on osteogenic lesions in zebrafish. These results provide a green, stable, cost-efficient, and reliable access to rapid discovery of drug leads, which verifiably benefits the design of nanocarbon-based biocomposites with increasingly advanced functionality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A new bergamotane sesquiterpenoid, named xylariterpenoid H ( 1 ), along with fourteen known compounds ( 2 - 15 ), were isolated from the crude extract of Aspergillus fumigatus , an endophytic fungus isolated from Delphinium grandiflorum L. Their structures were elucidated mainly by extensive analyses of NMR and MS spectroscopic data. In addition, the screening results of antibacterial and cytotoxic activities of compounds 1 - 15 showed that compound 4 displayed antibacterial activities against Staphylococcus aureus and MRSA (methicillin-resistant S. aureus ) with an MIC value of 3.12 µg/mL.

Objective: To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability., Methods: A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association., Results: Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects., Conclusion: Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup., Advances in Knowledge: This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

γ -aminobutyric acid (GABA) is closely related to the growth, development and stress resistance of plants. Combined with the previous study of GABA to promote the cotton against abiotic stresses, the characteristics and expression patterns of GABA branch gene family laid the foundation for further explaining its role in cotton stress mechanism. Members of GAD, GAB-T and SSADH (three gene families of GABA branch) were identified from the Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii genome. The GABA branch genes were 10 GAD genes, 4 GABA-T genes and 2 SSADH genes. The promoter sequences of genes mainly contains response-related elements such as light, hormone and environment.Phylogenetic analysis shows that GAD indicating that even in the same species, the homologous sequences in the family. The GABA-T gene of each cotton genus was in sum the family had gene loss in the process of dicotyledon evolution. SSADH families Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii were closely related to the dicot plants.GABA gene is involved in the regulation of salt stress and high temperature in Gossypium hirsutum.GABA attenuated part of the abiotic stress damage by increasing leaf protective enzyme activity and reducing reactive oxygen species production.This lays the foundation for a thorough analysis of the mechanism of GABA in cotton stress resistance., (© 2024. The Author(s).)

Two novel koninginin derivatives, koningipyridines A and B (1 and 2), along with four known compounds (3-6) were isolated from the EtOAc extract of the endophytic fungus Trichoderma koningiopsis SC-5. Among them, koningipyridine A featured an unprecedented pentacyclic ketal skeleton with the formation of a fascinating 6/6/5/6/5 fused ring system and shared a characteristic pyridine core, which represents the first example of nitrogen-containing koninginin-type natural product. Moreover, koningipyridine B was the first member in the koninginin family sharing a unique 6/6/5 dihydropyridine skeleton, and it was suggested to be the critical biosynthetic precursor of koningipyridine A. The structures of 1 and 2 were elucidated by the interpretation of 1D and 2D NMR spectroscopy, HRESIMS data, as well as theoretical calculations of 13 C NMR and electronic circular dichroism (ECD). Moreover, all isolates were screened for antimicrobial activities against Staphylococcus aureus, MRSA, and Escherichia coli as well as the cytotoxic effects against three cancer cell lines (A549, Hela, and HepG2)., (© 2024. The Author(s).)